POS1220 HUMORAL IMMUNE RESPONSE AGAINST BNT162b2 mRNA COVID-19 VACCINE IN JAPANESE RHEUMATIC DISEASE PATIENTS RECEIVING IMMUNOSUPPRESSIVE THERAPY: A MONOCENTRIC STUDY
Authors: K. Sugihara, R. Wakiya, H. Shimada, T. Kameda, S. Nakashima, M. Kato, T. Miyagi, M. Mizusaki, R. Mino, H. Dobashi
Journal: Annals of the Rheumatic Diseases (2022)

Background Patients with immune-mediated inflammatory diseases are inherently susceptible to infections and are at high risk of developing COVID-19. COVID-19 vaccination in patients with rheumatoid and musculoskeletal disease (RMD) is strongly recommended [1]. BNT162b2 is the most used COVID-19 vaccine in Japan. The safety and efficacy of this vaccine has been demonstrated in the general population [2], but patients receiving immunosuppressive therapy were excluded from the study. Although data on the immunogenicity of COVID-19 vaccine in the immunocompromised adult population is rapidly increasing, the immunogenicity of mRNA COVID-19 vaccine in RMD patients receiving medication has been reported in various and still inadequate ways. Furthermore, the immunogenicity of mRNA COVID-19 vaccine may vary depending on the medication. In addition, most of these data were reported from Western countries, and data on Japanese patients with RMD are limited. Objectives To investigate serum antibody titre against SARS-CoV-2 spike protein following BNT162b2 vaccination in Japanese RMD patients on various immunomodulatory treatment. Methods Two hundred and twelve RMD outpatients undergoing treatment at Kagawa University Hospital and 43 healthy volunteers, who had received two doses of BNT162b2, were included in the study. Serum sample was collected at least 14 days after the second dose. Antibody titer against SARS-CoV-2 spike protein in serum was measured by ELISA (Elecsys Anti-SARS-CoV-2 S RUO). We analyzed the relationship between clinical characteristics, including the type of disease and treatment of RMD, and antibody titer against SARS-CoV-2 spike protein. Results The antibody titer against SARS-CoV-2 spike protein in RMD patients was significantly lower than that in healthy subjects. In the analysis with therapeutic agents, the mean antibody titer in RMD patients treated with rituximab (RTX) was much lower than that in healthy controls. Patients treated with baricitinib, azathioprine, mycophenolate mofetil, abatacept, TNF inhibitors, cyclosporine, IL-6 inhibitors, methotrexate (MTX), or glucocorticoids (GC) had only moderately lower antibody titers. Patients treated with tacrolimus, an immunosuppressive drug commonly used for treatment in Japan, showed a slight decrease in antibody titer, but the difference was not significant compared with healthy subjects. IL-17 and IL-23 inhibitors did not impair the humoral response. In addition, the combination of MTX with various immunosuppressive agents reduced titers, although this was not statistically significant. Conclusion Many of the immunosuppressants impaired the immunogenicity to BNT162b2 in Japanese RMD patients. The degree of decline of antibody titers differed according to immunosuppressant. MTX potentially impairs the immunogenicity of BNT162b2 also in the case of concomitant use with other immunosuppressant. References [1]Curtis JR, et al. American College of Rheumatology Guidance for COVID-19 Vaccination in Patients With Rheumatic and Musculoskeletal Diseases: Version 3. Arthritis Rheumatol. 2021;73:e60-e75. [2]Polack FP, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383:2603–15. Figure 1. RMD diagnosis of study patients, n Table 1. Serum antibody titre against SARS-CoV-2 spike protein according to the use of immunosuppressive treatments in comparison with controls Immunosuppressive treatments, n Serum antibody titre, mean±SD, U/mL P value Control, n=43 939 ± 973 - Patients with RMD, n=212 572 ± 950 0.023 Without immunosuppressant, n=27 1074 ± 758 0.485 IL-17 or IL-23 inhibitors, n=7 1653 ± 2471 0.035 Tacrolimus, n=32 614 ± 920 0.095 GC, n=103 481 ± 927 0.009 MTX, n=78 310 ± 493 &lt;0.001 IL-6 inhibitors, n=10 303 ± 201 0.030 Cyclosporine, n=8 261 ± 228 0.035 TNF inhibitors, n=26 201 ± 252 &lt;0.001 Abatacept, n=10 186 ± 320 0.010 Mycophenolate mofetil, n=11 183 ± 357 0.007 Azathioprine, n=13 150 ± 159 0.003 Baricitinib, n=6 101 ± 97 0.021 RTX, n=6 20 ± 32 0.012 Disclosure of Interests None declared